Age-related macular degeneration (AMD) is a sudden worsening and distortion of central vision that progresses rapidly, typically with a course of only weeks or months. AMD is characterized by abnormalities in the macular area. The central area (or fovea) of the macula contains the highest density of cone photoreceptors in the retina and mediates high-acuity vision. The disease typically has a preclinical, asymptomatic phase, in which extracellular waste material accumulates in the space between the basement membrane (Bruch's membrane) and the epithelial layer, forming yellow-white spots known as drusen. Advanced forms of AMD includes both dry and wet (or “neovascular”) AMD. The dry form of AMD is far more common, but the wet form occurs simultaneously with the dry form in about 15% of cases. Dry AMD is characterized by progressive apoptosis of cells in the epithelial layer, in the overlying photoreceptor cells and in the underlying cells in the choroidal capillary layer. Wet AMD is characterized by choroidal neovascularization with vascular leakage into subretinal spaces.
AMD impairs central vision that is required for reading, driving, face recognition and fine visual tasks. Neurosensory detachment, retinal hemorrhages and retinal scarring gradually result in decreased visual function of photoreceptors in the central vision, eventually resulting in legal blindness, with preservation of peripheral vision. AMD is the most common cause of blindness among the elderly. Subjects with a family history of AMD and those who smoke have a higher risk than non-smokers and those with no family history. Nevertheless, subjects who have favorable risk profiles also develop the disease. Current therapeutic efforts and clinical trials are primarily aimed at halting the growth of the neovascular membrane in wet AMD, e.g., using angiogenesis (VEGF-A) inhibitors, laser photocoagulation and/or photodynamic therapy. Antioxidants can retard the progression of the disease.
Despite advances in treatment, AMD is still the most common cause of visual impairment in the developed world. Although genetic biomarkers are reasonably effective predictors of AMD risk and advanced AMD risk, there remains a significant need for new biomarkers that will improve the level of early diagnosis and enable treatments to be targeted to meet individual patient needs.